While much of the PI's previous research has been peripherally related to biomedicine, it was all done as an engineer's approach to solve biomedical problems. The materials were designed with only a basic understanding of the biological and medical needs. The proposed training opportunity would provide the PI with an in depth knowledge of some aspects of vascular medicine and physiology as well as added knowledge in mathematical modeling and peptide chemistry. The overall goal is to expand the PI's experience and training in biomedicine as well as in peptide chemistry and modeling to position her for a lifetime of research in biomedicine. Cardiovascular disease is the leading cause of death in the United States. The treatment of cardiovascular disease often involves surgically bypassing occluded segments of blood vessels with human saphenous vein grafts. The development of vein graft stenosis within 1 year after implantation occurs in up to 20-40% of grafts and frequently leads to end-organ failure, including myocardial infarction and extremity amputation. Short-term graft failure is due to technical problems and vasospasm during harvest and preparation. Long-term graft failure is due to a hyperplastic wound healing response, intimal hyperplasia. The purpose of this proposal is to develop a protein/peptide based therapeutic agent to enhance graft patency. The hypotheses of this investigation is that synthetic phosphorylated heat shock related protein human (HSP20) analogues (pHSP20) can be optimized and delivered in a controlled manner that will prevent vein graft spasm and intimal hyperplasia.
The specific aims are to: 1) Optimize TAT-pHSP20 as a functionally active biomolecule, la) Develop and synthesize a panel of analogues of the TAT-pHSP20 peptides, lb) Determine the bioactivity of the peptides ex vivo using strips of human saphenous vein grafts. 2) Develop and characterize controlled release systems for TAT-pHSP20 to ensure sustained delivery of the biomolecule in an effective therapeutic concentration. 2a) Determine the association and release of TAT from the heparin biogel. 2b) Determine the bioactivity of the biogel ex vivo in a muscle bath using strips of human saphenous vein grafts.
| Ward, Brian C; Kavalukas, Sandra; Brugnano, Jamie et al. (2011) Peptide inhibitors of MK2 show promise for inhibition of abdominal adhesions. J Surg Res 169:e27-36 |
| Ward, Brian C; Panitch, Alyssa (2011) Abdominal adhesions: current and novel therapies. J Surg Res 165:91-111 |
| Paderi, John E; Sistiabudi, Rizaldi; Ivanisevic, Albena et al. (2009) Collagen-binding peptidoglycans: a biomimetic approach to modulate collagen fibrillogenesis for tissue engineering applications. Tissue Eng Part A 15:2991-9 |
| Ward, Brian; Seal, Brandon L; Brophy, Colleen M et al. (2009) Design of a bioactive cell-penetrating peptide: when a transduction domain does more than transduce. J Pept Sci 15:668-74 |
